G proteins convert extracellular signals to intracellular events. Regulator of G protein signaling proteins (RGS) determine the response of the intracellular G protein signals by accelerating or blocking the G protein effects. One member of the RGS protein family, RGS2, has recently been described to be associated with aggressive and anxious behaviors in mice. The behavioral phenotypes link the RGS2 action to the serotonergic transmitter system in brain, which is involved in control of aggression and anxiety. We will investigate here the role of RGS2 for the physiology and the development of the serotonergic system by using RGS2(-/-) mice in combination with mice, where the serotonergic transmitter system expresses YFP under a serotonergic specific promotor. These mice will be used to identify serotonergic neurons during development and for electrophysiological recordings and will allow us to compare the neuronal networks between knock-out and wild-type animals. In addition we will create transgenic animals where RGS2 function is increased and/or decreased within the serotonergic system, to demonstrate that RGS2 has specific functions for regulating neuronal circuits involved in anxiety. Thus, the overall goal of this grant is to gain new insight into how neuronal circuits of the serotonergic system are altered in their physiology and development when the behavioral state of the animal is altered by the absence or presence of RGS2. PUBLIC HEALTH RELEVANCE: The importance of this study lies in the fact that nothing is known about the function of RGS proteins for regulating serotonergic signaling and that very little information is available on how the serotonergic system regulates itself. The study may therefore have major impact on our understanding of the regulation of anxiety states, but also other behaviors and physiological responses influenced and modulated by serotonin, such as aggression, circadian rhythm, blood pressure and breathing.